Liquid formulations are commonly used to administer active pharmaceutical ingredients. Liquid formulations may be swallowed, injected, or directly applied to a variety of different tissues. Many nasal and ophthalmic products are liquid formulations. Liquid formulations for oral administration are especially useful for patients who have difficulty swallowing solid dosage forms. Because liquids can be easily divided, it is much simpler to partition a liquid formulation into smaller doses than a solid formulation.
One of the simplest types of liquid formulation is an aqueous solution. However, many active pharmaceutical ingredients (“APIs”) are not sufficiently soluble in water to form practically useful solutions or those of desirable therapeutic strength. Additionally, many APIs are not stable in aqueous solution, decomposing upon long-term storage through a variety of pathways. For instance, many ester-group-containing pharmaceuticals, such as aspirin, undergo hydrolysis upon prolonged storage in water. Heterocycle-containing drugs, such as azacytidine and diazepam, undergo hydration followed by ring opening. Electrophilic drugs, such as cisplatin, can undergo nucleophilic exchange in the presence of water. Whether due to insufficient solubility, lack of stability, a combination of both, or another factor, many drugs cannot readily and conveniently, if at all, be formulated into aqueous solutions.
Although organic solvents can be used to solubilize certain drugs and minimize water-initiated decomposition, the use of organic solvents is not a practical or desirable solution in most pharmaceutical settings. Organic solvents are disfavored on regulatory grounds, due to toxicity, flammability, volatility, or environmental concerns. Furthermore, many organic solvents have an unpleasant odor or taste.
It is an object of this invention to provide liquid formulations of APIs, including poorly water-soluble or water-sensitive ones, for which the preparation of solutions or suspensions in water or organic solvents is difficult, undesirable, or impossible.
It is an object of the present invention to provide liquid formulations having a high concentration of the API(s), for example, in order to reduce the dosing size or frequency associated with the agent.
It is a further object of the invention to provide liquid formulations of APIs having enhanced stability relative to aqueous solutions of the active ingredient.
It is a still further object of the invention to provide transparent and pharmaceutically elegant liquid formulations of APIs that can be readily swallowed by a patient.